RELATED APPLICATIONS The present application claims the benefit of United States Provisional Patent Application No. 60/364,392, filed March 14,2002, entitled PHOSPHOROUS DEFICIENT OILS CONTAINING PHARMACEUTICALLY ACTIVE COMPOUNDS AND METHODS OF USING SAME, which is hereby incorporated by reference.

BACKGROUND OF THE INVENTION The dermal administration of pharmaceutically active compounds or cosmetic compounds involves the direct application of an effective amount of a pharmaceutically active formulation (s) to the skin, wherein the skin absorbs a portion of the pharmaceutically active compound which is then taken up by the blood stream. Such administration has long been known in the practice of medicine and continues to be an important technique in the delivery of pharmaceutically active compounds. For example, U. S. Pat. No. 4,286, 592 issued Sep. 1,1981 to Chandrasekaran, the Specification of which is hereby expressly incorporated herein by reference, shows a bandage for administering drugs to a user's skin consisting of an impermeable backing layer, a drug reservoir layer composed of a drug and a carrier, and a contact adhesive layer by which the bandage is affixed to the skin.

Such dermal administration offers many important advantages over other delivery techniques, such as injection, oral tablets and capsules. These advantages include being noninvasive (and therefore pose less risk of infection), avoiding first pass metabolism (metabolism of the drug in the liver when the drug is taken orally and absorbed through the gastrointestinal tract), and avoiding of high peaks and low valleys of concentration of pharmaceutically active compounds in a patient's bloodstream. In particular, high peaks and low valleys of concentration are typical in injection and oral administrations and are often associated with undesirable side effects and/or less than satisfactory intended effects.

While dermal drug delivery systems (DDDSs) work well in many aspects, current dermal drug delivery technology has some serious limitations, including: 1) the onset time being undesirably long for many DDDSs ; 2) the rate that the drug is taken into the systemic circulation or the targeted area (s) of the body cannot be easily varied once the DDDS is applied onto the skin and, when the steady state delivery rate is achieved, it cannot be easily changed; and 3) the skin permeability being so low that many drugs are excluded from dermal delivery because the amount of drug delivered is not high enough to reach a therapeutic level. In addition, temperature variations in the skin and the DDDS are believed to contribute to the variation of dermal absorption of drugs.

It is known that elevated temperature can increase the absorption of drugs through the skin. U. S. Pat. No. 4,898, 592, issued Feb. 6,1990 to Latzke et al. , relates to a device for the application of heated transdermally absorbable active substances which includes a carrier impregnated with a transdermally absorbable active

substance and a support. The support is a laminate made up of one or more polymeric layers and optionally includes a heat conductive element. This heat conductive element is used for distribution of the patient's body heat such that absorption of the active substance is enhanced. U. S. Pat. No. 4,230, 105, issued Oct.

28,1980 to Harwood, discloses a bandage with a drug and a heat-generating substance, preferably intermixed, to enhance the rate of absorption of the drug by a user's skin. Separate drug and heat-generating substance layers are also disclosed.

U. S. Pat. No. 4,685, 911, issued Aug. 11,1987 to Konno et al. , discloses a skin patch including a drug component, and an optional heating element for melting the drug- containing formulation if body temperature is inadequate to do so. Another area of administration involves delivering drugs in controlled/extended release form/formulations ("form/formulation") into the skin or tissues under the skin (the residing place for these form/formulations are hereinafter referred as"storage sites") which results in the drugs being released from the storage sites in a controlled/extended fashion.

The most common technique to deliver the form/formulations into the storage sites is by injection. Other techniques may also be used, such as implantation and forcing the form/formulation into the skin with high-speed hitting. However, once the form/formulation is delivered into the storage sites, it is usually difficult to alter the rate, known as the"release rate", that the drug is released from the form/formulation at the storage sites, and taken into the systemic circulation or the targeted area (s) of the body.

Yet another area of administration involves injecting drugs subcutaneously or intramuscularly. In some clinical situations, it is beneficial to accelerate the speed of drug absorption into the systemic circulation or other targeted areas (s) in the body after such injection.

Therefore, it would be advantageous to develop methods and apparatus to improve the dermal administration of pharmaceutically active compounds. It would also be advantageous to develop methods and apparatus to make dermal delivery possible for drugs which are currently excluded because of low skin permeability.

SUMMARY OF THE INVENTION The present invention includes a therapeutic composition that is useful for the alleviation of a human ailment. The composition preferably includes a transdermal delivery component and a pharmaceutically active component. In the presently preferred embodiment, the transdermal delivery component includes a phosphorous deficient oil. In a particularly preferred embodiment, the transdermal delivery component is emu oil.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT Before explaining at least one embodiment of the invention in detail by way of exemplary drawings, experimentation, results, and laboratory procedures, it is to be understood that the invention is not limited in its application to the details of construction and the arrangement of the components set forth in the following description or illustrated in the drawings, experimentation and/or results. The

invention is capable of other embodiments or of being practiced or carried out in various ways. As such, the language used herein is intended to be given the broadest possible scope and meaning; and the embodiments are meant to be exemplary-not exhaustive. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting.

The present invention overcomes the disadvantages and defects of the prior art by combining an effective amount of a pharmaceutically active compound with a transdermal delivery system comprising a phosphorous deficient oil. The composition of the present invention comprising a phosphorous deficient oil and a pharmaceutically active compound is utilized as a DDDS and is topically applied to the skin for delivery of the pharmaceutically active compound to a target site in a human body via skin penetration.

The terms"dermal drug delivery system" (or"DDDS"), "transdermal drug delivery system","penetrating transdermals","cosmetic transdermal delivery compounds"and"pharmaceutical dermal transport system"as used herein, refer to an article or apparatus containing pharmaceutically active compound (s) for delivery into the skin, the regional tissues under the skin, the systemic circulation, or other targeting site (s) in a human body via skin permeation.

The terms"transdermal delivery agents", "cosmetic dermal transport agents",<BR> "cosmetic transdermal delivery compounds", "pharmaceutical dermal transport agents", and"dermal transport enhancing compounds", as used herein, refer to an agent or compound that is combined with the pharmaceutically active compound (s)

that aid in transport of the pharmaceutically active compound (s) into the skin, the regional tissues under the skin, the systemic circulation, or other targeting site (s) in a human body via skin permeation.

Due to low permeability of the skin, onset times of conventional DDDSs are usually quite long, and often undesirably long. Thus, one aspect of the present invention is to provide methods and apparatus for using a phosphorous deficient oil as a transdermal delivery agent to increase the penetrability of the pharmaceutically active compound. The pharmaceutically active compound may be a compound that typically requires injection for delivery to a target site.

The term"skin", as used herein, is defined to include stratum corneum covered skin and mucosal membranes.

The term"drug", as used herein, is defined to include any pharmaceutically active compound including but not limited to compounds that treat diseases, injuries, undesirable symptoms, and improve or maintain health.

The terms"targeted area"or"targeted areas", as used herein, are defined to include a systemic bloodstream of a human body, areas of a human body which can be reached by a systemic bloodstream including, but not limited to muscles, brain, liver, kidneys, etc. , and body tissue regions proximate a location of an administered drug.

A variety of phosphorous deficient oils can be utilized in the composition of the present invention. Examples of such phosphorous deficient oils include, but are not limited to, phospho-lipid deficient oils, alpha hydroxy acids, amyl alcohol, angelica, apricot kernel oil, avocado oil, Bergamot, butyl alcohol, butylene glycol,

Calendula oil, camphor, Cedarwood, cinnamon, cineole, citric acids, clary sage, clove bud, coconut oil, cylcodextrins, DHEA (dehydroepiandosterone), dimethylformamide, dimethyl isosorbide, EFAs (essential fatty acids), emu oil, ethyl salicylate, evening primrose oil, eucalyptus oil, galactoxyloglucan, geranium oil, ginger, glycolic acid, grapeseed oil, hazelnut oil, hyaluronic acid, isopropyl alcohol, isopropyl salicylate, jojoba, juniper berry, Krill oil, lavender, lactic acids, lemon grass, magnesium ascorbyl phosphate, malic acid, marigold, marjoram, menthol, melaleuca tree oil, methyl salicylate, microemulsions, microspheres (microencapsulations), mineral oil, nanoemulsions, neroli, nutmeg, oleic acid, olive oil, oregano, peppermint, pine, polyethylene glycols, pregnenolone (PREG), propylene glycol, progesterone, rosemary, salicylic acid, sandalwood, sesame oil, sweet almond oil, tea tree, testosterone, thyme, urea, wheat germ oil, wintergreen, ylang ylang, and combinations thereof. In one embodiment of the present invention, the phosphorous deficient oil is emu oil.

In addition to the phosphorous-deficient oils listed herein, any underlying constituent or isolated component thereof, whether in its natural state or synthesized in a lab, may be utilized as the phosphorous-deficient oil of the present invention.

The terms"phosphorous deficient oil"and"phospholipid deficient oil"may be used interchangeably herein, and will be understood to also include the an underlying constituent or isolated component of a phosphorous-deficient oil as well as the entire phosphorous deficient oil.

A variety of pharmaceutically active drugs and drug classes can be utilized in the composition of the present invention. Such pharmaceutically active compound (s)

is selected based on the specific application and/or the individual patient's need. The pharmaceutically active compounds may be selected from the drug classes including, but not limited to, analgesics, anti-inflammatory agents, steroids, non-steroidal anti- inflammatory agents, anti-hypertensive agents, antispasmodics, anti-depressants, anti-psychotics, tranquilizers, antibiotics, antiviral agents, vaccines, anti-cancer agents, chemotherapeutic agents, immunosuppressive agents, local anesthetics, anti- emetics, anti-infectants, contraceptives, hormonal agents, anti-diabetic agents, cholinergic agonists, anti-cholinergics, anti-allergy agents, anti-migraine agents, antihistaminics, anti-asthma agents, cardiovascular agents, vasodilators, anti- thrombotic agents, diuretics, opiods, agents for smoking cessation, narcotic antagonists, anti-obesity agents, and combinations thereof.

Suitable pharmaceutically active compounds also include therapeutic and prophylactic agents. These include, but are not limited to, any therapeutically effective biological modifier. Such modifiers include, but are not limited to, subcellular compositions, cells, bacteria, viruses and molecules including, but not limited to, lipids, organics, proteins and peptides (synthetic and natural), peptide mimetics, hormones (peptide, steroid and corticosteroid), D and L amino acid polymers, oligosaccharides, polysaccharides, nucleotides, oligonucleotides and nucleic acids, including DNA and RNA, protein nucleic acid hybrids, small molecules and physiologically active analogs thereof. Further, the modifiers may be derived from natural sources or made by recombinant or synthetic means and include analogs, agonists and homologs. As used herein"protein"refers also to peptides and polypeptides. Such proteins include, but are not limited to, enzymes,

biopharmaceuticals, growth hormones, growth factors, insulin, monoclonal antibodies, interferons, interleukins and cytokines. Organics include, but are not limited to, pharmaceutically active chemicals with amino, imino and guanidino groups. Suitable steroid hormones include, but are not limited to, estrogen, progesterone, testosterone and physiologically active analogs thereof. Numerous steroid hormone analogs are known in the art and include, but are not limited to, estradiol, SH-135 and tamoxifen. As used herein, "nucleic acids"includes any therapeutically effective nucleic acids known in the art including, but not limited to DNA, RNA and physiologically active analogs thereof. The nucleotides may encode single genes or may be any vector known in the art of recombinant DNA including, but not limited to, plasmids, retroviruses and adeno-associated viruses.

Pharmaccutically active compounds may further include compositions containing prophylactic bioactive materials and carriers. Preferable compositions include immunogens such as vaccines. Suitable vaccines include, but are not limited to, live and attenuated viruses, nucleotide vectors encoding antigens, bacteria, antigens, antigens plus adjuvants, haptens coupled to carriers. Particularly preferred are vaccines effective against diphtheria, tetanus, pertussis, botulinum, cholera, Dengue, Hepatitis A, C and E, hemophilus influenza b, herpes virus, Hylobacterium pylori, influenza, Japanese encephalitis, meningococci A, B and C, measles, mumps, papilloma virus, pneumococci, polio, rubella, rotavirus, respiratory syncytial virus, Shigella, tuberculosis, yellow fever and combinations thereof. Vaccines may also be produced by molecular biology techniques to produce recombinant peptides or fusion proteins containing one or more portions of a protein derived from a

pathogen. For instance, fusion proteins containing the antigen of interest and the B subunit of cholera toxin have been shown to induce an immune response to the antigen of interest. Sanchez et al. (1989) Proc. Natl. Acad. Sci. USA 86: 481-485.

Preferably, when an immunogenic composition is utilized as the pharmaceutically active compound, the immunogenic composition contains an effective amount of an adjuvant sufficient to enhance the immune response to the immunogen. Suitable adjuvants include, but are not limited to, aluminum salts, squalene mixtures (SAF-1), muramyl peptide, saponin derivatives, mycobacterium cell wall preparations, monophosphoryl lipid A, mycolic acid derivatives, nonionic block copolymer surfactants, Quil A, cholera toxin B subunit, polyphosphazene and derivatives, and immunostimulating complexes (ISCOMs) such as those described by Takahashi et al. (1990) Nature 344: 873-875. For veterinary use and for production of antibodies in animals, mitogenic components of Freund's adjuvant can be used. As with all immunogenic compositions, the immunologically effective amounts of the immunogens must be determined empirically. Factors to be considered include the immunogenicity, whether or not the immunogen will be complexed with or covalently attached to an adjuvant or carrier protein or other carrier, route of administration and the number of immunizing doses to be administered. Such factors are known in the vaccine art, and it is well within the skill of immunologists to make such determinations without undue experimentation.

A partial list of biologically active agents or drugs that may be utilized as the pharmaceutically active compound of the present invention includes: antibacterial agents; peptides ; polypeptides; antibacterial peptides; antimycobacterial agents;

antimycotic agents; antiviral agents; antiparastic agents; antifungal agents; antiyeast agents; anti-diabetic agents, such as insulin; hormonal peptides; cardiovascular agents; hormonal peptides; cardiovascular agents; narcotic antagonists; analgesics; anesthetics; insulins; steroids including HIV therapeutic drugs (including protease inhibitors) and AZT; estrogens; progestins; gastrointestinal therapeutic agents; non- steroidal anti-inflammatory agents; antiarthritic agents; parasympathomimetic agents; psychotherapeutic agents; tranquilizers; anti-anxiety agents; cholinergic agonists; decongestants; sedative-hypnotics; non-estrogenic steroids; sympathomimetic agents; anti-migraine drugs; electrolyte replacements; ergot alkaloids; anti-inflammatory agents; prostaglandins; cytotoxic drugs; antigens; antibodies; enzymes; growth factors; immunomodulators; immunosuppressive drugs ; chemotherapeutic agents; pheromones; prodrugs; psychotropic drugs; nicotine; anti blood clotting drugs; appetite suppressants/stimulants and combinations thereof; contraceptive agents, including estrogens such as diethyl silbestrol, 17-beta-estradiol, estrone, ethinyl estradiol, mestranol, progestins such as norethindrone, norgestryl, ethynodiol diacetate, lynestrenol, medroxyprogesterone acetate, dimethisterone, megestrol acetate, chlormadinone acetate, norgestimate, norethisterone, ethisterone, melentate, melengestrol, norethynodrel, and spermicidal compounds such as nonyphenoxypolyoxyethylene glycol; benzethonium chloride; chlorindanol; gastrointestinal therapeutic agents such as aluminum hydroxide, calcium carbonate, magnesium carbonate, sodium carbonate and the like; non- steroidal antifertility agents; psychotherapeutic agents; major tranquilizers such as chloropromaquine HCL, clozapine, mesoridazine, metiapine, reserpine, thioridazine

and the like; minor tranquilizers such as chlordiazepoxide, diazepam, meprobamate, temazepam and the like; rhinological decongestants; sedative-hypnotics such as codeine, phenobarbital, sodium pentobarbital, sodium secobarbital and the like; other steroids such as testosterone and testosterone propionate; sulfonomides ; vaccines; vitamins and nutrients; essential amino acids; essential fats; anti-HIV agents, including AZT; antimalarials such as 4-aminoquinolines, 8-aminoquinolines, pyrimethamine and the like; anti-migraine agents such as mazindol; phentermine ; anti-Parkinson agents such as L-dopa; antispasmodics such as atropine; methscopolamine bromide; antispasmodics and anticholinergic agents such as bile therapy, digestants, enzymes and the like; antitussives such as dextromethorphan and noscapine; bronchodilators; cardiovascular agents such as anti-hypertensive compounds; anti-thrombolytic agents; Rauwolfia alkaloids; coronary, cerebral and peripheral vasodilators; nitroglycerin; organic nitrites; pentaerythriotetra nitrate; electrolyte replacements such as potassium chloride; ergotalkaloids such as ergotamine with and without caffeine; hydrogenated ergot alkaloids; dihydroergocristine methanesulfate ; dihydroergocornine methanesulfonate ; dihydroergokroyptine methaneusulfate and combinations thereof ; alkaloids such as atropine sulfate; Belladonna; hyoscine hydrobromide; analgesics; narcotics such as codeine, dihydrocodienone, meperidine, morphine and the like; narcotic antagonists; non-narcotics such as salicylates, aspirin, acetaminophen, d-propoxyphene and the like; antibiotics such as the cephalosporins including ceflacorand cefuroxime, chloranphenical, gentamicin, Kanamycin A, Kanamycin B, the penicillins ampicillin and amoxicillin, streptomycin A, antimycin A, chloropamtheniol, metromidazole,

oxytetracycline penicillin G, the tetracyclines including minocycline, fluoro- quinolones including ciprofloxacin, ofoxacin, macrolides including clarithromycin, frythromycin, aminioglycosides including gentamicin, amikacin, tobramycin and kanamycin, beta-lactams including ampacillin, polymyxin-B, amphotercin-B, aztrofonam, chloramphenicol, fusidans, lincosamides, metronidazole, nitro- furantion, imipenem/cilastin, quinolones and the like; systemic antibodies including rifampin ; polygenes; sulfunamides ; trimethoprim; glycopeptides including vancomycin; teicoplanin and imidazoles; anti-cancer agents; including anti-kaposi's sarcoma; anti-convulsants such as mephenytoin; phenobarbital; trimethadione; anti- emetics such as triethylperazine; antihistamines such as chlorophinazine, dimenhydrinate, diphenhydramine, perphenazine, tripelennamine and the like; anti- inflammatory agents such as hormonal agents; hydrocortisone; prednisolone; prednisone; non-hormonal agents; allopurinol; agents for smoking cessation; water- soluble hormone drugs; antibiotics; antitumor agents; anti inflammatory agents; antipyretics; analgesics; local anesthetics; antitussives; expectorants; sedatives; muscle relaxants; antiepileptics; anticulcer agents; antidepressants; antiallergic drugs; cardiotonics; antiarrhythmic drugs; vasodilators; antihypertensives; diuretics; anticoagulants; and anti narcotics; in the molecular wight range of 100-100,000 daltons; indomethacin; phenylbutazone; prostaglandins; cytotoxic drugs such as thiotepa; chloramucil; cyclophosphamide; melphala; nitrogen mustard; methotrexate; antigens such as proteins; glycoproteins; synthetic peptides; carbohydrates; synthetic polysaccharides; lipids; glycolipids; lipopolysaccharides (LPS); synthetic lipopolysaccharides and with or without

attached adjuvants such as synthetic muramyl dipeptide derivatives; antigens of such microorganisms as Neisseha gonorrhea ; Mycobacterium tuberculosis ; Picarinii Pnfumonia ; Herpes virus (humonis types 1 and 2); Herpes zoster; Candida albicans ; Candida tropicalis ; Trichomonas vaginalis ; Haemophilus vaginalis ; Group B Streptoccoccus ; Microplasma hominis ; Haemophilus ducreyi ; Granuloma inguinale; Lymphopathia venerum ; Treponema palidum ; Brucella abortus ; Brucella melitensis ; Brucella suis ; Brucella canis ; Campylobacter fetus ; Campylobacer fetus intestinalis ; Leptospira pomona ; Listeria monocytogenes ; Brucella ovis ; Equine herpes virus 1; Equine arteritis virus; IBR-IBP virus; Chlamydiapsittaci ; Trichomonasfoetus ; Toxoplasma gondii ; Escherichia coli ; Actinobadllus equuli ; Salmonella abortusovis ; Salmonella abortus-equi ; Pseudomonas aeruginosa ; Corynebacterium ; Pseudomonas pyogenes ; Actinobadllus seminis ; Mycoplasma bovigenitalium ; Aspergillus fumigatus ; Absidia ramosa ; Trypanosoma equiperdum ; Babesia caballi ; Clostridium tetani ; antibodies which counteract the above microorganisms; and enzymes such as ribonuclease; neuraminidase; trypsin; glycogen phosphorylase; lactic dehydrogenase; hyaluronidase; adenosinetriphosphase; alkaline phosphatase; amino peptidase; chymotrypsin ; amylase ; muramidase; acrosomal proteinase; diesterase; glutamic acid dehydrogense; succinic dehydrogenase; beta- glycophosphatase lipase; ATP-ase; gamma-glutamyl transpeptidase; steroid-beta-ol- dehydrogenase; and combinations thereof.

The novel delivery system of this invention is applicable to all categories of active substances capable of being used for the prevention and/or treatment of human, animal and plant diseases. This delivery system is also applicable to the

design of novel diagnostic tests. Additionally, it can be useful for the delivery to a subject of a polyfunctional mixture or cocktail formulation of encapsulated active (i. e. biologically) substances for the prevention and/or treatment of diseases the same or different. The encapsulated formulation ingredients would be comprised of multiple drugs, multiple vaccines or a combination thereof.

The present invention contemplates the formulation of disease specific compositions for the prevention and/or treatment of diseases and/or ailments which include: viral infections; bacterial infections; fungal infections; yeast infections; parasitic infections and more specific diseases and/or ailments, such as AIDS ; Alzheimer's dementia; angiogenesis diseases; ulcers; asthma; atopic dermatitis ; psoriasis; basal cell carcinoma; benign prostatic hypertrophy; blood substitute; blood substitute in surgery patients; blood substitute in trauma patients; cachexia; Campylobacter infection; Cancer; pneumonia; sexually transmitted diseases (STDs); viral diseases; Candida albicans ; candidiasis; pain in cancer; pancreatic cancer; Parkinson's disease; peritumoral brain edema; postoperative adhesions (prevention); proliferative diseases; prostate cancer; ragweed allergy; renal disease; restenosis; rheumatoid arthritis; rheumatoid arthritis; allergies; rotavirus infection; scalp psoriasis; septic shock; small-cell lung cancer; solid tumors; stroke; thrombosis; type I diabetes; type I diabetes w/kidney transplants; type II diabetes; visceral leishmaniasis; malaria; periodontal or gum disease; cardiac rhythm disorders; central nervous system disorders; cervical dystonia (spasmodic torticollis); choridal neovascularization; chronic hepatitis A, B and C; colitis associated with antibiotics; colorectal cancer; coronary artery thrombosis; cryptosporidiosis; Cryptosporidium

parvum diarrhea; cystic fibrosis; cytomegalovirus disease; depression; social phobias; panic disorder; diabetic complications; diabetic eye disease; diarrhea associated with antibiotics; erectile dysfunction; genital herpes; graft-vs-host disease in transplant patients; growth hormone deficiency; head and neck cancer; head trauma; stroke; heparin neutralization after cardiac bypass; hepatocellular carcinoma; HIV; HIV infection; Huntington's disease; CNS diseases; hypercholesterolemia; hypertension; inflammation; inflammation and angiogenesis; inflammation in cardiopulmonary bypass; influenza; migraine headache; interstitial cystitis; Kaposi's sarcoma; lung cancer; melanoma; Molluscum contagiosum; multiple sclerosis; neoplastic meningitis from solid tumors; non-small cell lung cancer; organ transplant rejection; osteoarthritis; rheumatoid arthritis; osteoporosis; drug addiction; shock; ovarian cancer; and pain.

The method of using the composition of the present invention comprises providing a composition comprising a therapeutically effective amount of at least one pharmaceutically active compound and an effective amount of at least one phosphorous deficient oil, and topically applying such composition to the patient's skin (wherein the patient may be an animal, such as a human) in an amount effective to cover at least an affected area wherein the composition is able to penetrate the patient's skin and deliver the at least one pharmaceutically active compound to a target site.

Changes may be made in the construction and the operation of the various components, elements and assemblies described herein or in the steps or the sequence of steps of the methods described herein without departing from the spirit and scope of the invention.